Oxidative Medicine and Cellular Longevity

Review Article

The Role of Stress-Induced O-GlcNAc Protein Modification in the Regulation of Membrane Transport

Table 1

O-GlcNAc-influenced membrane or membrane-associated transport proteins.


Protein	Function	Evidence for direct influence by O-GlcNAc	Evidence for indirect influence by O-GlcNAc	Reference

Potassium voltage-gated channel subfamily KQT member 3 (KCNQ3)	Voltage-dependent K⁺ channel	+	−	[97]
Potassium voltage-gated channel subfamily KQT member 2 and 5 (KCNQ2, KCNQ5)	Voltage-dependent K⁺ channel	MS hit	Form complex with KCNQ3	[93, 98]
Small conductance calcium-activated potassium channel protein 2 and 3 (KCNN2, KCNN3)	Voltage-independent calcium-activated K⁺ channel	MS hit	−	[93]
Calcium-activated potassium channel subunit alpha-1 (KCNMA1)	Calcium-activated K⁺ channel	MS hit	−	[93]
Potassium voltage-gated channel subfamily A member 4 (KCNA4)	Voltage-dependent K⁺ channel	MS hit	−	[93]
Voltage-gated sodium channels	Sodium transport	MS hit	Ankyrin G (link the cytoplasmic domains of integral proteins to cytoskeletal proteins)	[93, 100]
Sodium/potassium-transporting ATPase subunit alpha-2 and alpha-3	Plasma membrane sodium-potassium exchanger	MS hit	−	[93]
Stromal interaction molecule 1 (STIM1)	Ca²⁺ store depletion triggered Ca²⁺ influx in nonexcitable cells	+	−	[96]
Voltage-dependent calcium channels (CACNB3, CACNG3, CACNA1B, CACNA1A, CACNA1G)	Voltage-dependent Ca²⁺ channels in murine synapses	MS hit	−	[93]
Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA)	Endoplasmic Ca²⁺ reuptake. Playing a role in cardiac muscle contractility	+	Phospholamban (repressor of SERCA)	[94, 95]
Voltage-dependent anion-selective channel protein 1 and 3 (VDAC1, VDAC3)	Voltage-dependent anion channels in the outer mitochondrial and cell membrane	+	Bcl-2 (inhibits mPTP opening possibly by interaction with VDAC)	[59, 93, 151, 152]
Chloride channel-2 (ClC-2)	Cl⁻ channel	−	Sp1 (transcription factor)	[102]
Synapsin I	Regulation of synaptic vesicle release	+	−	[32, 114]
Alpha-synuclein	Regulation of neurotransmitter release	+	Identified O-GlcNAc sites influence its aggregation properties	[118]
Adaptor protein-1 (AP-1)	Endocytosis	−	Interaction with synergin gamma that has been identified as O-GlcNAc target	[37, 119, 120]
Piccolo (PCLO)	Cycling of synaptic vesicles	+	−	[116]
Amyloid-β precursor protein (APP)	Synapse formation	+	−	[22]
Solute carrier family 2, facilitated glucose transporter member 4 (GLUT4)	Glucose transporter	+	Munc18c (GLUT4 vesicle protein, influencing its translocation)	[109, 110]
Solute carrier family 2, facilitated glucose transporter member 1 (GLUT1)	Glucose transporter	−	HIF-1α (induces the transcription of GLUT1. O-GlcNAc affects the degradation of HIF-1α.)	[111]
Nucleoporins (Nups)	Nuclear transport	+	−	[26, 143–146]
Nup153	Nuclear transport for proteins and RNA	+	−	[160]
Importin α5	Nuclear transport receptor for proteins	−	Mediates the nuclear import of OGT	[37, 161]
Beta-catenin	Intracellular adhesion and transcriptional coactivator	+	−	[31]
Nuclear factor-κB (NFκB)	Transcriptional factor	+	−	[33, 48, 140, 141]

Specific proteins are selected and included in the table based on either direct, published evidence for O-GlcNAc modification, or indirect evidence (e.g., a molecular partner of the protein is known to be O-GlcNAcylated, or O-GlcNAc influences the expression of the protein). We considered finding O-GlcNAc protein only by mass spectrometry screening combined with various enrichment techniques (e.g., wheat germ agglutinin binding) as direct—albeit weak—evidence and indicated in the table as “MS hit.”